The overall objective of this proposal is to study the beneficial effects of Ginkgo biloba on HIV therapeutic vaccines. Our preliminary studies demonstrate that a component from the Ginkgo biloba, Ginkgolide A, can act to enhance the differentiation and activation of CD 14+ monocyte-derived Dendritic cells (DC), indicating a positive modulating function of Ginkgolide A in eliciting immune responses. Furthermore, it has been shown that DC vaccines could be a promising strategy for treating people with chronic HIV-1 infection. The unifying hypothesis is that immunization with mixtures of HIV virus-like particles (VLPs) and Ginkgo biloba components may enhance the immune responses induced by HIV VLPs alone. We propose to investigate the adjuvant effect of each different component in Ginkgo Biloba in enhancing both the humoral and the cellular immune responses in a CD4 KO mouse model. Two Specific Aims are proposed in our studies. Studies in Aim 1 are designed to determine if Ginkgo biloba enhances SIV Gag and HIV Env specific immune responses in HA/SHIV VLP immunized mouse model. We will investigate the adjuvant effect of different components in Ginkgo biloba in enhancing both humoral and cellular immune responses in a CD4 KO mouse model which are intranasally immunized with HA/SHIV VLPs with daily treatment by Ginkgo biloba component(s). Studies in Aim 2 are designed to compare molecular mechanism of Ginkgo biloba modulating DC activation and antigen-presentation function. We will also investigate signal transduction pathways activated by Ginkgo biloba treatment. In future studies, the component(s) in Ginkgo biloba that has the most potent effect in enhancing immune responses against HIV antigens will be advanced for evaluation in SHIV infected rhesus monkeys with low CD4+ T cell counts. We will compare disease progression with VLP-immunized SHIV infected monkeys to evaluate efficacy of our Ginkgo biloba and VLPs mixture as a therapeutic vaccine. The results obtained from the proposed research will help to provide insights into the enhancement effect of Ginkgo biloba on HIV therapeutic vaccine, and to further elucidate the mechanism and benefits of using complementary and alternative medicine (CAM). Furthermore, it will have the potential to initiate translational and early phase clinical trials to investigate this CAM and VLPs approach to treat HIV/AIDS and its complications. [unreadable] [unreadable]